A few of the islet

A few of the islet-specific proteins identified in the present study have previously been described in various contexts of pancreatic islets, i.e. PTPRN, SCG5, SCGN, SNAP25 and SNED1, validating the search algorithm applied and supporting the notion that also the novel proteins identified are indeed beta cell-specific. Presence of buy ivermectin against PTPRN (also called IA-2) is widely used in the diagnosis of autoimmune diabetes and serves as a predictive marker for high-risk subjects. The expression is induced by glucose, insulin and cAMP-generating agents [27] and deletion of PTPRN in mice resulted in mild glucose intolerance and decreased glucose-responsive insulin secretion [28]. SCG5 plays a role in regulating pituitary hormone secretion [29]. Previous studies have suggested that SCG5 partly colocalizes with all pancreatic islet hormones [30], which is in concordance with the results of the present study. Studies on mice with mutations in the promoter of SCG5, suggest a role in glucagon production and secretion [31]. In addition, genetic variation in SCG5 has been suggested to worsen glucose intolerance and insulin resistance in humans with severe obesity [32]. The calcium-binding protein SCGN is expressed in cytoplasmic vesicles and on secretory vesicle membranes. Previous studies have shown that the expression level of SCGN is decreased at onset of diabetes in rats, suggesting a role in the pathogenesis of T1D. In the present study, SCGN stained all islets strongly in all subjects, including patients with long-standing T1D disease, and could hence be a potential marker of total islet mass. SNAP25 plays a role in synaptic functions and neurotransmitter release and may be involved in regulating calcium entry at the site of exocytosis, which may affect cell excitability and insulin secretion [33], [34]. Increased gene transcription mediated through the secreted protein SNED1 has recently been suggested to contribute to beta cell dysfunction in insulin resistance [35]. HMGXB3 is a member of the HMGB protein family that contains the DNA-binding high-mobility group (HMG) and is hence thought to play a role in DNA-replication and DNA repair [36], [37]. The exact function of HMGXB3 has not been previously characterized and no studies have showed selective expression of HMGB proteins in pancreatic islets. Two of the studied antibodies (C4ORF18 and QRFPR) stained neither alpha nor beta cells but approximately 10% of the islet cells. C4ORF18 is an unknown glycoprotein and potential transmembrane protein that belongs to the FAM198 family, while QRFPR is a G-protein coupled receptor and transmembrane protein that modulates intracellular calcium levels. Previous studies on QRFPR have shown expression mainly in cells of the CNS [38]. In addition, studies have proved that 26RFa, a shorter peptide of QRFPR, markedly increased food intake in mice [39] and inhibited insulin secretion in rats [40], which suggest a functional role in the pancreas. Methods for assessing islets and beta cells are still mainly indirect, for example measurements of oral glucose stimulation, C-peptide levels and insulin secretion. Accurate assessment of beta cell mass in a direct, non-invasive manner would enable analysis of changes in beta cell mass at onset and during progression of both T1D and T2D and provide an important tool to evaluate the efficacy of various anti-diabetic treatment protocols. Non-invasive measurement of beta cell mass could also allow for a more precise endpoint in the evaluation of various replacement therapies as for islet transplantation. A promising tool to monitor beta cells non-invasively is by molecular imaging, for example PET, which is a technique that has the requirements needed for imaging of small cell numbers as it is highly sensitive and quantitative. Since satisfactory targets for PET tracers are still lacking, i.e. available surface markers, identification of new potential markers for that purpose is needed. Therefore, in the present study, we used antibody-based proteomics to identify membrane bound proteins that is the first step in the process towards imaging of beta cells.